Acetyl-CoA

Acetyl-CoA

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Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

, used in many biochemical reactions. Its main function is to convey the carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

 atom
Atom
The atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...

s within the acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...

 group to the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

 to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester
Thioester
Thioesters are compounds with the functional group C-S-CO-C. They are the product of esterification between a carboxylic acid and a thiol. Thioesters are widespread in biochemistry, the best-known derivative being acetyl-CoA.-Synthesis:...

 between coenzyme A
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...

 (a thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

) and acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...

 (an acyl
Acyl
An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...

 group carrier). Acetyl-CoA is produced during the second step of aerobic cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

, pyruvate decarboxylation, which occurs in the matrix
Mitochondrial matrix
In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...

 of the mitochondria. Acetyl-CoA then enters the citric acid cycle.

Acetyl-CoA is also an important component in the biogenic synthesis of the neurotransmitter acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

. Choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....

, in combination with acetyl-CoA, is catalyzed by the enzyme choline acetyltransferase
Choline acetyltransferase
Choline acetyltransferase is an enzyme that is synthesized within the body of a neuron. It is then transferred to the nerve terminal via axoplasmic flow. The role of choline acetyltransferase is to join Acetyl-CoA to choline, resulting in the formation of the neurotransmitter acetylcholine...

 to produce acetylcholine and a coenzyme a
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...

 byproduct.

Pyruvate dehydrogenase and pyruvate formate lyase reactions


The oxidative conversion of pyruvate into acetyl-CoA is referred to as the pyruvate dehydrogenase reaction. It is catalyzed by the pyruvate dehydrogenase complex. Other conversions between pyruvate and acetyl-CoA are possible. For example, pyruvate formate lyase
Pyruvate formate lyase
Pyruvate formate lyase is an enzyme found in Escherichia coli and other organisms. It helps regulate anaerobic glucose metabolism. Using radical non-redox chemistry, it catalyzes the reversible conversion of pyruvate and coenzyme-A into formate and acetyl-CoA...

 disproportionates pyruvate into acetyl-CoA and formic acid
Formic acid
Formic acid is the simplest carboxylic acid. Its chemical formula is HCOOH or HCO2H. It is an important intermediate in chemical synthesis and occurs naturally, most notably in the venom of bee and ant stings. In fact, its name comes from the Latin word for ant, formica, referring to its early...

.

Fatty acid metabolism


In animals, acetyl-CoA is essential to the balance between carbohydrate metabolism
Carbohydrate metabolism
Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms....

 and fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...

 metabolism (see fatty acid synthesis
Fatty acid synthesis
Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and malonyl-CoA precursors through action of enzymes called fatty acid synthases...

). In normal circumstances, acetyl-CoA from fatty acid metabolism feeds into the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

, contributing to the cell's energy supply. In the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, when levels of circulating fatty acids are high, the production of acetyl-CoA from fat breakdown exceeds the cellular energy requirements. To make use of the energy available from the excess acetyl-CoA, ketone bodies
Ketone bodies
Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...

 are produced, which can then circulate in the blood.

In some circumstances, this can lead to the presence of very high levels of ketone bodies in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

, a condition called ketosis
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...

. Benign dietary ketosis can safely occur in people following low-carbohydrate diet
Low-carbohydrate diet
Low-carbohydrate diets or low-carb diets are dietary programs that restrict carbohydrate consumption usually for weight control or for the treatment of obesity. Foods high in digestible carbohydrates are limited or replaced with foods containing a higher percentage of proteins and fats...

s, which cause fats to be metabolised as a major source of energy. This is different from ketosis brought on as a result of starvation, and from ketoacidosis
Ketoacidosis
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....

, a dangerous condition that can affect diabetics.

In plants, de novo fatty acid synthesis occurs in the plastids. Many seeds accumulate large reservoirs of seed oils to support germination
Germination
Germination is the process in which a plant or fungus emerges from a seed or spore, respectively, and begins growth. The most common example of germination is the sprouting of a seedling from a seed of an angiosperm or gymnosperm. However the growth of a sporeling from a spore, for example the...

 and early growth of the seedling before it is a net photosynthetic organism. Fatty acids are incorporated into membrane lipids, the major component of most membranes.

Other reactions

  • Two acetyl-CoA molecules can be condensed
    Condensation reaction
    A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...

     to create acetoacetyl-CoA
    Acetoacetyl-CoA
    Acetoacetyl CoA is the precursor of HMG-CoA in the Mevalonate pathway, which is essential for cholesterol synthesis. It also takes a similar role in the ketone bodies synthesis pathway of the liver...

    , the first step in the HMG-CoA/mevalonic acid pathway, leading to synthesis of isoprenoids. In animals, HMG-CoA is a vital precursor to cholesterol
    Cholesterol
    Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

     and ketone body
    Ketone bodies
    Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...

     synthesis.
  • Acetyl-CoA is also the source of the acetyl group incorporated onto certain lysine residues of histone and nonhistone proteins in the posttranslational modification acetylation
    Acetylation
    Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...

    , a reaction catalyzed by acetyltransferases.
  • In plants and animals, cytosolic acetyl-CoA is synthesized by ATP citrate lyase
    ATP citrate lyase
    ATP citrate lyase is an enzyme that represents an important step in fatty acid biosynthesis. This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates to the production of fatty acids.-Function:ATP citrate lyase is the primary enzyme...

    . When glucose is abundant in the blood of animals, it is converted via glycolysis
    Glycolysis
    Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...

     in the cytosol
    Cytosol
    The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

     to pyruvate, and then to acetyl-CoA in the mitochondrion. The excess of acetyl-CoA results in production of excess citrate
    Citrate
    A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...

    , which is exported into the cytosol to give rise to cytosolic acetyl-CoA.
  • Acetyl-CoA can be carboxylated in the cytosol by acetyl-CoA carboxylase
    Acetyl-CoA carboxylase
    Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase and carboxyltransferase...

    , giving rise to malonyl-CoA
    Malonyl-CoA
    Malonyl-CoA is a coenzyme A derivative.-Functions:It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis....

    , a substrate required for synthesis of flavonoids and related polyketides, for elongation of fatty acids to produce waxes, cuticle
    Cuticle
    A cuticle , or cuticula, is a term used for any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticles" are non-homologous; differing in their origin, structure, function, and chemical composition...

    , and seed oils in members of the Brassica
    Brassica
    Brassica is a genus of plants in the mustard family . The members of the genus may be collectively known either as cabbages, or as mustards...

     family, and for malonation of proteins and other phytochemicals.
  • In plants, these include sesquiterpene
    Sesquiterpene
    Sesquiterpenes are a class of terpenes that consist of three isoprene units and have the molecular formula C15H24. Like monoterpenes, sesquiterpenes may be acyclic or contain rings, including many unique combinations...

    s, brassinosteroid
    Brassinosteroid
    Brassinosteroids are a class of polyhydroxysteroids that have been recognized as a sixth class ofplant hormones. These were first explored nearly forty years ago when Mitchell et al. reported promotion in stem elongation and cell division by the treatment of organic extracts of rapeseed pollen...

    s (hormones), and membrane sterol
    Sterol
    Sterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol...

    s.

Interactive pathway map


Click on genes, proteins and metabolites below to visit Gene Wiki pages and related Wikipedia articles. The pathway can be downloaded and edited at WikiPathways.

See also

  • Citric acid cycle
    Citric acid cycle
    The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

  • HMG-CoA reductase pathway
    HMG-CoA reductase pathway
    The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent route or isoprenoid pathway, is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria...

  • Fatty acid metabolism
    Fatty acid metabolism
    Fatty acids are an important source of energy and adenosine triphosphate for many cellular organisms. Excess fatty acids, glucose, and other nutrients can be stored efficiently as fat. Triglycerides yield more than twice as much energy for the same mass as do carbohydrates or proteins. All cell...

  • Acyl CoA
  • Acetyl Co-A synthetase
    Acetyl Co-A synthetase
    Acetyl—CoA synthetase or Acetate—CoA ligase is an enzyme involved in metabolism of carbon sugars. It is in the ligase class of enzymes, meaning that it catalyzes the formation of a new chemical bond between two large molecules.-Reaction:...

  • Malonyl-CoA decarboxylase
    Malonyl-CoA decarboxylase
    Malonyl-CoA decarboxylase is an enzyme associated with Malonyl-CoA decarboxylase deficiency.It catalyzes the conversion of malonyl-CoA into acetyl-CoA and carbon dioxide.To some degree, it reverses the action of Acetyl-CoA carboxylase....


External links